TY  - JOUR
A1  - Salihoglu, Rana
A1  - Srivastava, Mugdha
A1  - Liang, Chunguang
A1  - Schilling, Klaus
A1  - Szalay, Aladar
A1  - Bencurova, Elena
A1  - Dandekar, Thomas
T1  - PRO-Simat: Protein network simulation and design tool
JF  - Computational and Structural Biotechnology Journal
N2  - PRO-Simat is a simulation tool for analysing protein interaction networks, their dynamic change and pathway engineering. It provides GO enrichment, KEGG pathway analyses, and network visualisation from an integrated database of more than 8 million protein-protein interactions across 32 model organisms and the human proteome. We integrated dynamical network simulation using the Jimena framework, which quickly and efficiently simulates Boolean genetic regulatory networks. It enables simulation outputs with in-depth analysis of the type, strength, duration and pathway of the protein interactions on the website. Furthermore, the user can efficiently edit and analyse the effect of network modifications and engineering experiments. In case studies, applications of PRO-Simat are demonstrated: (i) understanding mutually exclusive differentiation pathways in Bacillus subtilis, (ii) making Vaccinia virus oncolytic by switching on its viral replication mainly in cancer cells and triggering cancer cell apoptosis and (iii) optogenetic control of nucleotide processing protein networks to operate DNA storage. Multilevel communication between components is critical for efficient network switching, as demonstrated by a general census on prokaryotic and eukaryotic networks and comparing design with synthetic networks using PRO-Simat. The tool is available at https://prosimat.heinzelab.de/ as a web-based query server.
KW  - network simulation
KW  - protein analysis
KW  - signalling pathways
KW  - dynamic protein-protein interactions
KW  - optogenetics
KW  - oncolytic virus
KW  - DNA storage
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350034
SN  - 2001-0370
VL  - 21
ER  - 
TY  - JOUR
A1  - Chubanov, Vladimir
A1  - Ferioli, Silvia
A1  - Wisnowsky, Annika
A1  - Simmons, David G.
A1  - Leitzinger, Christin
A1  - Einer, Claudia
A1  - Jonas, Wenke
A1  - Shymkiv, Yuriy
A1  - Gudermann, Thomas
A1  - Bartsch, Harald
A1  - Braun, Attila
A1  - Akdogan, Banu
A1  - Mittermeier, Lorenz
A1  - Sytik, Ludmila
A1  - Torben, Friedrich
A1  - Jurinovic, Vindi
A1  - van der Vorst, Emiel P. C.
A1  - Weber, Christian
A1  - Yildirim, Önder A.
A1  - Sotlar, Karl
A1  - Schürmann, Annette
A1  - Zierler, Susanna
A1  - Zischka, Hans
A1  - Ryazanov, Alexey G.
T1  - Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival
JF  - eLife
N2  - Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.
KW  - signalling pathways
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164987
VL  - 5
ER  -